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Objectives: This study examined the effects of acute normoxic and hypoxic exposure on neuromuscular and hemodynamic physiological responses performed during dynamic step muscle actions., Methods: Thirteen recreationally active men (mean ± SD age: 21.2 ± 2.9 yrs) performed dynamic leg extensions unilaterally under Normoxic (FiO 2  = 21 %) and Hypoxic (FiO 2  = 13 %) conditions in a randomized order at 20 %, 40 %, 60 %, 80 %, and 100 % of their maximal strength. Electromyographic (EMG) amplitude, EMG frequency, (Oxygenated and Deoxygenated hemoglobin; Oxy Hb , Deoxy Hb) , Total hemoglobin (Total Hb ), and skeletal muscle tissue oxygenation status (StO 2 ) were measured from the vastus lateralis during all contractions., Results: There were no detectable differences in the neuromuscular responses between normoxia and hypoxia for EMG amplitude (p = 0.37-0.74) and frequency (p = 0.17-0.83). For EMG amplitude there were general increases with intensity (p < 0.01-0.03). EMG frequency remained similar from 20% to 80% and then increased at 100 % effort (p = 0.02). There was no significant difference in patterns of responses for Oxy Hb (p = 0.870) and Total Hb (p = 0.200) between normoxia and hypoxia. StO 2 (p = 0.028) decreased and Deoxy Hb (p = 0.006) increased under hypoxia compared to normoxia during dynamic step muscle actions performed in a randomized order., Conclusion: Unlike fatigue, acute hypoxemia in an unfatigued state does not impact the localized neuromuscular responses, but minimally impacts the hemodynamic responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Older adults may present to the emergency department (ED) with agitation, a symptom often resulting in chemical sedation and physical restraint use which carry significant risks and side effects for the geriatric population. To date, limited literature describes the patterns of differential restraint use in this population., Design, Setting, Participants, and Measurements: This retrospective cross-sectional study used electronic health records data from ED visits by older adults (age ≥65 years) ranging 2015-2022 across nine hospital sites in a regional hospital network. Logistic regression models were estimated to determine the association between patient-level characteristics and the primary outcomes of chemical sedation and physical restraint., Results: Among 872,587 ED visits during the study period, 11,875 (1.4%) and 32,658 (3.7%) encounters involved the use of chemical sedation and physical restraints respectively. The populations aged 75-84, 85-94, 95+ years had increasingly higher odds of chemical sedation [adjusted odds ratios (AORs) 1.35 (95% CI 1.29-1.42); 1.82 (1.73-1.91); 2.35 (2.15-2.57) respectively] as well as physical restraint compared to the 65-74 group [AOR 1.31 (1.27-1.34); 1.55 (1.50-1.60); 1.69 (1.59-1.79)]. Compared to the White Non-Hispanic group, the Black Non-Hispanic and Hispanic/Latinx groups had significantly higher odds of chemical sedation [AOR 1.26 (1.18-1.35); AOR 1.22 (1.15-1.29)] and physical restraint [AOR 1.12 (95% CI 1.07-1.16); 1.22 (1.18-1.26)]., Conclusion: Approximately one in 20 ED visits among older adults resulted in chemical sedation or physical restraint use. Minoritized group status was associated with increasing use of chemical sedation and physical restraint, particularly among the oldest old. These results may indicate the need for further research in agitation management for historically marginalized populations in older adults., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Central odontogenic fibromas (COF) are rare, benign tumors derived from dental mesenchymal tissue that may occur in the maxilla or mandible. This report describes primary and recurrent COF in the mandible of a patient with nevoid basal cell carcinoma syndrome (NBCCS)., Study Design: A 36-year-old African American male presented with a COF and its recurrence 17 months later. Tissue pieces were obtained from both occurrences with IRB-approved signed consent. Collected tissue pieces were dissected; one portion was formalin-fixed and paraffin-embedded, and the other was cultured for the isolation of cell populations from the primary (COdF-1) and recurrent (COdF-1a) tumors. Quantification real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and DNA sequencing were used for gene and protein analysis of the primary tumor and cell populations., Results: Histopathologic analysis of the tumor showed sparse odontogenic epithelial cords in fibrous connective tissue, and qRT-PCR analysis of tumor and cell populations (COdF-1 and COdF-1a) detected VIM, CK14, CD34, CD99 and ALPL mRNA expression. Protein expression was confirmed by immunohistochemistry. CD34 expression in primary tissues was higher than in tumor cells due to tumor vascularization. DNA sequencing indicated the patient had PTCH1 mutations., Conclusions: Histopathology, mRNA, and protein expression indicate the rare occurrence of COF in a patient with mutated PTCH1 gene and NBCCS., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Disclosures None of the authors reported any disclosures.

SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays. Mass spectrometry and enzyme-linked immunosorbent assay experiments were used to identify and measure the abundance of proteins that specifically bind to SARS-CoV-2 antigens. Immunoglobulin (Ig)A specific to SARS-CoV-2 antigens was detectable in over 83% of the convalescent saliva samples. We found that concentrations of anti-receptor-binding domain IgA >500 pg/µg total protein in saliva correlate with reduced viral infectivity in vitro. However, there is a dissociation between the salivary IgA response to SARS-CoV-2, and systemic IgG titers in convalescent COVID-19 patients. Then, using an innovative technique known as spike-baited mass spectrometry, we identified novel spike-binding proteins in saliva, most notably vimentin, which correlated with increased viral infectivity in vitro and could serve as a therapeutic target against COVID-19., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Machine learning techniques for clinical applications are evolving, and the potential impact this will have on clinical neurology is important to recognize. By providing a broad overview on this growing paradigm of clinical tools, this article aims to help healthcare professionals in neurology prepare to navigate both the opportunities and challenges brought on through continued advancements in machine learning. This narrative review first elaborates on how machine learning models are organized and implemented. Machine learning tools are then classified by clinical application, with examples of uses within neurology described in more detail. Finally, this article addresses limitations and considerations regarding clinical machine learning applications in neurology., Competing Interests: Declaration of Competing Interest A. L. Weathers has a non-compensated relationship as the chair of the Epic Neurology Specialty Steering Board (Epic Systems) and has received personal compensation in the range of $5000 to $9000 for serving as a CME question writer and interviewer for the American Academy of Neurology (AAN). S. L. Lewis has a non-compensated relationship as Secretary General of the World Federation of Neurology and has received compensation as a Director of the American Board of Psychiatry and Neurology and has received compensation from the AAN as former editor of Continuum: Lifelong Learning in Neurology. C. M. Smith has nothing to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background: Social factors like race and insurance affect transplant outcomes. However, little is known in pediatric heart transplantation. We hypothesized that race and insurance coverage impact listing and waitlist outcomes across eras., Methods: Data from the Pediatric Heart Transplant Society multi-center registry prospectively collected between January 1, 2000-December 31, 2019 were analyzed. Patients were divided by race as Black, White and other and by insurance coverage at listing (US governmental, US private and non-US single payer systems (UK, Canada). Clinical condition at listing and waitlist outcomes were compared across races and insurance coverages. Categorical variables were compared using a chi-square test and continuous variables using the Wilcoxon rank sum test. Risk factors for waitlist mortality were examined using multiphase parametric hazard modeling. A sensitivity analysis using parametric hazard explored the interaction between race and insurance., Results: At listing, compared to Whites (n = 5391) and others (n = 1167), Black patients (n = 1428) were older, more likely on US governmental insurance and had cardiomyopathy as the predominant diagnosis (p < 0.0001). Black patients were more likely to be higher status at listing, in hospital, on inotropes or a ventricular assist device (p < 0.0001). Black patients had significantly shorter time on the waitlist compared to other races (p < 0.0001) but had higher waitlist mortality (p = 0.0091), driven by the earlier era (2000-2009) (p = 0.0005), most prominently within the US private insurance cohort (p = 0.015). Outcomes were not different in other insurance cohorts or in the recent era (2010-2019)., Conclusion: Black children are older and sicker at the time of listing, deteriorate more often and face a higher wait list mortality, despite a shorter waitlist period and favorable clinical factors, with improvement in the recent era associated with the recent US healthcare reforms. The social construct of race appears to disadvantage Black children by limiting referral, consideration or access to pediatric cardiac transplantation., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

A heart-healthy lifestyle, beginning at an early age and sustained throughout life, may reduce risk for cardiovascular disease in youth. Among youth with moderate to severe dyslipidemia and/or those with familial hypercholesterolemia, lipid-lowering medications are often needed for primary prevention of cardiovascular disease. However, lifestyle interventions are a foundation for youth with dyslipidemia, as well as those without dyslipidemia. There are limited data supporting the use of dietary supplements in youth with dyslipidemia at this time. A family-centered approach and the support of a multi-disciplinary healthcare team, which includes a registered dietitian nutritionist to provide nutrition counseling, provides the best opportunity for primary prevention and improved outcomes. While there are numerous guidelines that address the general nutritional needs of youth, few address the unique needs of those with dyslipidemia. The goal of this National Lipid Association Clinical Perspective is to provide guidance for healthcare professionals caring for youth with disorders of lipid and lipoprotein metabolism, including nutritional guidance that complements the use of lipid lowering medications., Competing Interests: Conflicts of interest Disclosures for CMBS during the prior 24 months include a speaker honorarium from Cardiometabolic Congress. ALP received consulting fees paid to institution from Novartis during the prior 24 months. DPW received consulting fees from Alexion during the prior 24 months. LW, JB, JC, CK, SLL, ASS, GS, and ALW have no relevant disclosures., (Copyright © 2022. Published by Elsevier Inc.)

Google Street View's 'Time Machine' feature holds promise for longitudinal street audits of built and natural environments for urban health research. As images are only available when Google collected data, differential image availability over time and place could bias audit data quality. We assessed image availability at 2000 randomly selected locations within the Bronx and San Diego from which Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants were recruited. In the Bronx, a mean of 7.4 images (95% CI: 7.2,7.5) were available at each location, and 63% of those locations had imagery in 2007 and 2019. In San Diego, fewer images were available (mean 5.4, 95% CI: 5.2,5.6) especially on minor streets (mean 4.4, 95% CI: 4.1,4.6). Image availability was more spatially clustered in San Diego (Moran's I 0.14) than the Bronx (Moran's I 0.04). Differential image availability may affect precision of neighborhood change estimates assessed by longitudinal virtual audit., (Copyright © 2021. Published by Elsevier Ltd.)

Insect-resistant crops feed much of the world, using reduced carbon inputs and providing much greater economic returns on investment. Newer, more efficient efforts are urgently needed to speed development of insect-resistant plants before a projected 30% global population increase. Plant resistance researchers must employ genotyping by sequencing and high-throughput phenotyping to identify, map and track resistance genes. In contrast to maize, rice, vegetables and wheat, limited progress has occurred to develop meaningful levels of pest resistance in cassava, cowpea and pigeonpea - major sources of nutrition for nearly 1 billion people. A knowledge void exists about the effects of climate change (elevated CO 2 ) on resistant plants, necessitating efforts to understand this stress. Collaborations with social scientists, extension specialists, economists, spatiotemporal modelers, ecologists, and virologists will be required to develop better ways to integrate insect resistant plants into integrated crop pest management programs., (Copyright © 2020 The Author. Published by Elsevier Inc. All rights reserved.)

There has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been well-characterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Granulocyte recruitment to the pulmonary compartment is a hallmark of progressive tuberculosis (TB). This process is well-documented to promote immunopathology, but can also enhance the replication of the pathogen. Both the specific granulocytes responsible for increasing mycobacterial burden and the underlying mechanisms remain obscure. We report that the known immunomodulatory effects of these cells, such as suppression of protective T-cell responses, play a limited role in altering host control of mycobacterial replication in susceptible mice. Instead, we find that the adaptive immune response preferentially restricts the burden of bacteria within monocytes and macrophages compared to granulocytes. Specifically, mycobacteria within inflammatory lesions are preferentially found within long-lived granulocytes that express intermediate levels of the Ly6G marker and low levels of antimicrobial genes. These cells progressively accumulate in the lung and correlate with bacterial load and disease severity, and the ablation of Ly6G-expressing cells lowers mycobacterial burden. These observations suggest a model in which dysregulated granulocytic influx promotes disease by creating a permissive intracellular niche for mycobacterial growth and persistence.

The purpose of this study was to compare isokinetic peak torque and the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG), amplitude (AMP) and mean power frequency (MPF) for bilateral (BL) versus unilateral (UL), maximal, isokinetic leg extensions. Eleven recreationally trained women (Mean ± SD: age 22.9 ± 0.9 yrs; body mass 60.5 ± 10.1 kg; height 167.2 ± 6.4 cm) performed 50 maximal, BL and UL isokinetic leg extensions at 60° s -1 on separate days. Electromyographic and MMG signals from the vastus lateralis of the nondominant leg were recorded. Five separate 2 (Condition [BL and UL]) × 10 (Repetitions [5-50]) repeated measures ANOVAs were performed to examine normalized EMG AMP, EMG MPF, MMG AMP, MMG MPF, and isokinetic torque. The results indicated no significant interactions or main effects for EMG AMP and MMG AMP. There were significant interactions for normalized isokinetic peak torque (p < 0.001, η 2 p  = 0.493) and MMG MPF (p = 0.003, η 2 p  = 0.234). For EMG MPF, there was no significant interaction, but significant main effects for Condition (p = 0.003, η 2 p  = 0.607) and Repetitions (p < 0.001, η 2 p  = 0.805). The current findings demonstrated greater performance fatigability for UL than BL leg extensions. Both modalities exhibited similar patterns of neuromuscular responses that were consistent with the Muscular Wisdom hypothesis., Competing Interests: Declaration of Competing Interest All authors report no conflicts of interest for this manuscript. Additionally, there were no external funding sources., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous studies indicate coastlines are at risk of wastewater contamination from injection wells, cesspools, and septic systems. In this study, common marine algae were used to ground-truth modeled loading of wastewater-derived N to coastlines of O'ahu, Hawai'i. Macroalgae were collected and/or deployed at 118 sites and analyzed for tissue δ 15 N and N %. Wastewater source locations were used to estimate wastewater-derived N in groundwater with the modeling software MT3DMS/MODFLOW. Algal bioassays identified six coastal regions subjected to elevated wastewater-derived N loading. In a case study, submarine groundwater discharge (estimated by 222 Rn mass balance) was related to wastewater loading from onsite sewage disposal systems (OSDS) and municipal wastewater injection wells in Waimānalo. The highest 222 Rn-derived SGD rate and N flux were 21.4 m 3 /m/d and 62.6 g/m/d, respectively. The results of this study suggest that OSDS and injection wells discharge substantial volumes of wastewater and N across broad regions of coastal O'ahu., (Copyright © 2019. Published by Elsevier Ltd.)

An emerging novel therapeutic agent for major depressive disorder, minocycline, has the potential to influence both gut microbiome and inflammatory status. The present study showed that chronic high fat diet feeding led to changes in both behaviour and the gut microbiome in male mice, without an overt inflammatory response. The diet-induced behavioural changes were characterised as increased immobility in the forced swim test and changes in locomotor activities in the open field test. Minocycline significantly altered the gut microbiome, rendering a community distinctly different to both untreated healthy and diet-affected states. In contrast, minocycline did not reverse high fat diet-induced changes in behaviour., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The consumption of dietary salt (NaCl) is controlled by neuronal pathways that are modulated by endogenous opioid signalling. The latter is disrupted by chronic use of exogenous opioid receptor agonists, such as morphine. Therefore, opioid dependence may influence salt consumption, which we investigated in two complimentary studies in humans and mice., Methods: Human study: three groups were recruited: i. Individuals who are currently opioid dependent and receiving opioid substitution treatment (OST); ii. Previously opioid dependent individuals, who are currently abstinent, and; iii. Healthy controls with no history of opioid dependence. Participants tasted solutions containing different salt concentrations and indicated levels of salt 'desire', salt 'liking', and perceptions of 'saltiness'. Mouse study: preference for 0.1 M versus 0.2 M NaCl and overall levels of salt consumption were recorded during and after chronic escalating morphine treatment., Results: Human study: Abstinent participants' 'desire' for and 'liking' of salt was shifted towards more highly concentrated salt solutions relative to control and OST individuals. Mouse study: Mice increased their total salt consumption during morphine treatment relative to vehicle controls, which persisted for 3 days after cessation of treatment. Preference for 'low' versus 'high' concentrations of salt were unchanged., Conclusion: These findings suggest a possible common mechanistic cross-sensitization to salt that is present in both mice and humans and builds our understanding of how opioid dependence can influence dietary salt consumption. This research may help inform better strategies to improve the diet and overall wellbeing of the growing number of individuals who develop opioid dependence., (Copyright © 2019. Published by Elsevier B.V.)

For more than 50 years DEET (N,N-Diethyl-m-toluamide) has been considered the gold standard of repellents. It is applied to the skin or clothing to deter mosquitoes and other blood-sucking invertebrate pests from approaching and/or settling, and ultimately it provides temporary protection from bites. Despite rampant global use, surprisingly little is understood about DEET's mode of action and the molecular targets of the active ingredient. Furthermore, the theories into its mechanism for repellency are largely based off fruit fly and mosquito research. Since ticks possess a unique sensory structure, the Haller's organ, the specific genes and pathways associated with DEET avoidance may differ from insects. In these studies, we collected American dog ticks (Dermacentor variabilis) from four natural populations within Manitoba, Canada. We first carried out behavior assays, which showed DEET effectively repelled the ticks. RNA sequencing revealed that DEET caused a rapid and substantial reduction in the abundance of transcripts encoding cytochrome P450 and acetylcholinesterase genes, which gradually recovered over the 24 h time course. Finally, enzymatic kinetics provided functional support for DEET's role as an effective inhibitor of P450 s. While many facets of its mode of action remain to be worked out, our study provides valuable insights into the molecular underpinnings of DEET's repellence in ticks., (Crown Copyright © 2019. Published by Elsevier GmbH. All rights reserved.)

The proficiency of cancer cells to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) is a key determinant in predicting response to targeted therapies such as PARP inhibitors. The RAD51 paralogs work as multimeric complexes and act downstream of BRCA1 to facilitate HR. Numerous epidemiological studies have linked RAD51 paralog mutations with hereditary cancer predisposition. Despite their substantial links to cancer, RAD51 paralog HR function has remained elusive. Here we identify isoform 1 as the functional isoform of RAD51D, whereas isoform 4 which has a large N-terminal deletion (including the Walker A motif), and isoform 6 which includes an alternate exon in the N-terminus, are non-functional. To determine the importance of this N-terminal region, we investigated the impact of cancer-associated mutations and SNPs in this variable RAD51D N-terminal region using yeast-2-hybrid and yeast-3-hybrid assays to screen for altered protein-protein interactions. We identified two cancer-associated mutations close to or within the Walker A motif (G96C and G107 V, respectively) that independently disrupt RAD51D interaction with XRCC2. We validated our yeast interaction data in human U2OS cells by co-immunoprecipitation and determined the impact of these mutations on HR-proficiency using a sister chromatid recombination reporter assay in a RAD51D knock-out cell line. Our investigation reveals that the interaction of RAD51D with XRCC2 is required for DSB repair. By characterizing the impact of cancer-associated mutations on RAD51D interactions, we aim to develop predictive models for therapeutic sensitivity and resistance in patients who harbor similar mutations in RAD51D., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT., Methods: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN26184967., Findings: Between Sept 1, 2014, and Oct 1, 2016, we randomly assigned 226 patients; 112 to VOT and 114 to DOT. Overall, 131 (58%) patients had a history of homelessness, imprisonment, drug use, alcohol problems or mental health problems. In the ITT analysis, 78 (70%) of 112 patients on VOT achieved ≥80% scheduled observations successfully completed during the first 2 months compared with 35 (31%) of 114 on DOT (adjusted odds ratio [OR] 5·48, 95% CI 3·10-9·68; p<0·0001). In the restricted analysis, 78 (77%) of 101 patients on VOT achieved the primary outcome compared with 35 (63%) of 56 on DOT (adjusted OR 2·52; 95% CI 1·17-5·54; p=0·017). Stomach pain, nausea, and vomiting were the most common adverse events reported (in 16 [14%] of 112 on VOT and nine [8%] of 114 on DOT)., Interpretation: VOT was a more effective approach to observation of tuberculosis treatment than DOT. VOT is likely to be preferable to DOT for many patients across a broad range of settings, providing a more acceptable, effective, and cheaper option for supervision of daily and multiple daily doses than DOT., Funding: National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The selection of epoch lengths affects the time and frequency resolution of electromyographic (EMG) and mechanomyographic (MMG) signals, as well as decisions regarding the signal processing techniques to use for determining the power density spectrum. No previous studies, however, have examined the effects of epoch length on parameters of the MMG signal. The purpose of this study was to examine the differences between epoch lengths for EMG amplitude, EMG mean power frequency (MPF), MMG amplitude, and MMG MPF from the VL and VM muscles during MVIC muscle actions as well as at each 10% of the time to exhaustion (TTE) during a continuous isometric muscle action of the leg extensors at 50% of MVIC. During the MVIC trial, there were no significant (p > 0.05) differences between epoch lengths (0.25, 0.50, 1.00, and 2.00-s) for mean absolute values for any of the EMG or MMG parameters. During the submaximal, sustained muscle action, however, absolute MMG amplitude and MMG MPF were affected by the length of epoch. All epoch related differences were eliminated by normalizing the absolute values to MVIC. These findings supported normalizing EMG and MMG parameter values to MVIC and utilizing epoch lengths that ranged from 0.25 to 2.00-s., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study used a combined electromyographic, mechanomyographic, and force approach to identify electromechanical delay (EMD) from the onsets of the electromyographic to force signals (EMD E-F ), onsets of the electromyographic to mechanomyogrpahic signals (EMD E-M ), and onsets of mechanomyographic to force signals (EMD M-F ). The purposes of the current study were to examine: (1) differences in EMD E-M , EMD M-F , and EMD E-F from the vastus lateralis between maximal isokinetic and maximal concentric isometric leg extensions; and (2) the effects of fatigue and recovery on EMD E-M , EMD M-F , and EMD E-F . These EMD measures were obtained from twelve men during maximal concentric isokinetic and isometric leg extensions pretest, posttest, and after 3-min and 5-min of recovery from 25 maximal isokinetic leg extensions at 60°s -1 . The results indicated no differences between maximal isokinetic and isometric muscle actions for EMD E-M , EMD M-F , or EMD E-F during the pretest, posttest, 3-min recovery, and 5-min recovery measurements. These findings support the comparison of voluntary EMD measures between studies with different modes of exercise as long as the methodology for the determination of EMD are consistent. There were, however, fatigue-induced pretest to posttest increases in EMD E-M , EMD M-F , and EMD E-F which remained elongated after 3-min of recovery, but returned to pretest values after 5-min of recovery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study used a combined electromyographic, mechanomyographic, and force approach to identify electromechanical delay (EMD) from the onsets of the electromyographic to force signals (EMD E-F ), onsets of the electromyographic to mechanomyogrpahic signals (EMD E-M ), and onsets of mechanomyographic to force signals (EMD M-F ). The purposes of the current study were to examine: (1) the differences in EMD E-F , EMD E-M , and EMD M-F from the vastus lateralis during maximal, voluntary dynamic (1 repetition maximum [1-RM]) and isometric (maximal voluntary isometric contraction [MVIC]) muscle actions; and (2) the effects of fatigue on EMD E-F , EMD M-F , and EMD E-M . Ten men performed pretest and posttest 1-RM and MVIC leg extension muscle actions. The fatiguing workbout consisted of 70% 1-RM dynamic constant external resistance leg extension muscle actions to failure. The results indicated that there were no significant differences between 1-RM and MVIC EMD E-F , EMD E-M , or EMD M-F. There were, however, significant fatigue-induced increases in EMD E-F (94% and 63%), EMD E-M (107%), and EMD M-F (63%) for both the 1-RM and MVIC measurements. Therefore, these findings demonstrated the effects of fatigue on EMD measures and supported comparisons among studies which examined dynamic or isometric EMD measures from the vastus lateralis using a combined electromyographic, mechanomyographic, and force approach., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

It is commonly held that language is largely lateralized to the left hemisphere in most individuals, whereas spatial processing is associated with right hemisphere regions. In recent years, a number of neuroimaging studies have yielded conflicting results regarding the role of language and spatial processing areas in processing language about space (e.g., Carpenter, Just, Keller, Eddy, & Thulborn, 1999; Damasio et al., 2001). In the present study, we used sparse scanning event-related functional magnetic resonance imaging (fMRI) to investigate the neural correlates of spatial language, that is; language used to communicate the spatial relationship of one object to another. During scanning, participants listened to sentences about object relationships that were either spatial or non-spatial in nature (color or size relationships). Sentences describing spatial relationships elicited more activation in the superior parietal lobule and precuneus bilaterally in comparison to sentences describing size or color relationships. Activation of the precuneus suggests that spatial sentences elicit spatial-mental imagery, while the activation of the SPL suggests sentences containing spatial language involve integration of two distinct sets of information - linguistic and spatial., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Given the well-documented symptom overlap between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD), careful evaluation of potential differentiation and overlap is critical for accurate diagnostic decisions. Although research has considered the use of symptom checklists and parent/teacher report questionnaires for symptom differentiation, standardized observational methods, typically utilized in the context of ASD evaluation, have received less attention. The present study examined the continuum of communication and social interaction impairment for youth diagnosed with ASD and ADHD, as indexed by the Autism Diagnostic Observation Schedule (ADOS). Participants were 209 youth ages 3 to 18 years with ASD, ADHD, Dual Diagnosis (ASD+ADHD) or No Diagnosis. Differences across diagnostic groups were observed for mean communication and social interaction total scores on the ADOS, with the highest scores (i.e., greater impairment) observed for the ASD group and lowest scores for the ADHD and No Diagnosis groups. Results provide the first evidence for use of the ADOS for distinguishing youth who have ADHD alone versus ASD alone or co-occurring ASD+ADHD. Findings are discussed in light of implications for clinical practice and future research.

The purposes of the present study were to examine the effects of electrode placements over, proximal, and distal to the innervation zone (IZ) on electromyographic (EMG) amplitude (RMS) and frequency (MPF) responses during: (1) a maximal voluntary isometric contraction (MVIC), and; (2) a sustained, submaximal isometric muscle action. A linear array was used to record EMG signals from the vastus lateralis over the IZ, 30mm proximal, and 30mm distal to the IZ during an MVIC and a sustained isometric muscle action of the leg extensors at 50% MVIC. During the MVIC, lower EMG RMS (p>0.05) and greater EMG MPF (p<0.05) values were recorded over the IZ compared to away from the IZ, however, no differences in slope coefficients for the EMG RMS and MPF versus time relationships over, proximal, and distal to the IZ occurred. Thus, the results of the present study indicated that during an MVIC, EMG RMS and MPF values recorded over the IZ are not comparable to those away from the IZ. However, the rates of fatigue-induced changes in EMG RMS and MPF during sustained, submaximal isometric muscle actions of the leg extensors were the same regardless of the electrode placement locations relative to the IZ., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Many red cell polymorphisms are a result of selective pressure by the malarial parasite. Here, we add another red cell disease to the panoply of erythrocytic changes that give rise to resistance to malaria. Erythrocytes from individuals with erythropoietic protoporphyria (EPP) have low levels of the final enzyme in the heme biosynthetic pathway, ferrochelatase. Cells from these patients are resistant to the growth of Plasmodium falciparum malarial parasites. This phenomenon is due to the absence of ferrochelatase and not an accumulation of substrate, as demonstrated by the normal growth of P falciparum parasites in the EPP phenocopy, X-linked dominant protoporphyria, which has elevated substrate, and normal ferrochelatase levels. This observation was replicated in a mouse strain with a hypomorphic mutation in the murine ferrochelatase gene. The parasite enzyme is not essential for parasite growth as Plasmodium berghei parasites carrying a complete deletion of the ferrochelatase gene grow normally in erythrocytes, which confirms previous studies. That ferrochelatase is essential to parasite growth was confirmed by showing that inhibition of ferrochelatase using the specific competitive inhibitor, N-methylprotoporphyrin, produced a potent growth inhibition effect against cultures of P falciparum. This raises the possibility of targeting human ferrochelatase in a host-directed antimalarial strategy., (© 2015 by The American Society of Hematology.)

Objective: The aims of proximal hypospadias repair are good cosmetic outcomes with low rates of complication, with a low number of operative exposures, before the age of genital difference realisation. Neo-urethral fistula and stenosis are well recognised complications; with international rates of 3.8-16% and 1.3-15.6% respectively. We present the key steps of the second of a two staged repair in video format., Method: Video recording of the procedure performed on an 18-month-old with mid-penile hypospadias is presented. The steps are described; the importance of tension free tubularisation, layered urethral closure, suture technique, vascularised prepucal graft technique, optimal glanuloplasty, and penile shaft skin repair are highlighted., Result: The child was brought back to the day ward for catheter removal at 7 days; follow-up in clinic showed good postoperative appearance. This technique has been performed on 31 boys with a fistula rate and stenosis rate favourable to the literature., Conclusion: We demonstrate a two-stage technique by video format for proximal hypospadias which is reproducible and gives results comparable to the literature., (Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: As waiting time for heart transplantation has increased, ventricular assist devices have become critical for "bridging" patients with end-stage heart failure. Because most reported post-discharge experience is with left ventricular assist devices (LVAD), we sought to evaluate the safety and feasibility of home discharge on paracorporeal biventricular assist devices (BIVAD)., Methods: We retrospectively reviewed the hospital course and post-discharge outcomes of 46 consecutive patients who received paracorporeal VADs as bridge to transplant. The success of home discharge was assessed by frequency and reasons for hospital readmission and survival to transplant., Results: Thirty patients (65%) were successfully transferred from the intensive care unit and considered candidates for discharge. Of the 26 patients discharged home, 11 were supported with an LVAD and 15 with BIVADs. Median duration of support until transplant, explant, or death did not differ significantly between LVAD or BIVAD patients (91 days vs 158 days; p = 0.09). There were 26 readmissions for medical or device-related complications; 10 in 7 LVAD patients and 16 in 10 BIVAD patients, with no difference in median length of stay (17 days vs 25 days; p = 0.67). Out of hospital duration of support was similar between LVAD and BIVAD patients (61 days vs 66 days; p = 0.87) as were 6-month and 1-year event-free survival rates (p = 0.49)., Conclusions: Outcomes were similar in patients bridged to transplant on home paracorporeal BIVAD versus LVAD support. We recommend discharge for stable patients demonstrating device competency and adequate home care regardless of the need for univentricular or biventricular paracorporeal support., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The mechanism behind why patients with primary ciliary dyskinesia (PCD) exhibit low nasal and exhaled nitric oxide (NO) remains unknown. One hypothesis is that reduced NO biosynthesis is caused by a defect in one or more NO synthases (NOSs). In healthy cells, the biosynthesis of NO is increased following exposure to respiratory pathogens. Here, we aimed to investigate whether ciliated epithelial cells from patients with PCD increase NO production following pneumococcal infection., Methods: Human respiratory epithelium was cultured to a basal or ciliated cell phenotype using submerged or air-liquid interface cultures, respectively. Cells were exposed to media or pneumococci until cells became damaged (&lt; 4 h). Apical fluids were collected prior and following infection, and NO production was determined using chemiluminescence. NOS gene expression was determined using real-time quantitative polymerase chain reaction., Results: Levels of NO and NOS2 gene expression increased significantly following infection of healthy ciliated epithelial cells but not basal cells. No increase in NO was seen in ciliated cell cultures from patients with PCD, and NOS2 gene expression remained unchanged from baseline., Conclusions: These results suggest that the biosynthesis of NO in ciliated cells from patients with PCD is abnormal following early bacterial challenge, suggesting an abnormality in the function of inducible NOS in PCD.

The brains of Long Evans shaker (les) rats, a model of dysmyelination, and their age- matched controls were studied by ex-vivo q-space diffusion imaging (QSI) and diffusion tensor imaging (DTI). The QSI and DTI indices were computed from the same acquisition. The les and the control brains were studied at different stages of maturation and disease progression. The mean displacement, the probability for zero displacement and kurtosis were computed from QSI data while the fractional anisotropy (FA) and the eigenvalues were computed from DTI. It was found that all QSI indices detect the les pathology, at all stages of maturation, while only some of the DTI indices could detect the les pathology. The QSI mean displacement was larger in the les group as compared with their age-matched controls while the probability for zero displacement and the kurtosis were both lower all indicating higher degree of restriction in the control brains. Since all the DTI eigenvalues were higher in the les brains as compared to controls, the less efficient DTI measure for discerning the les pathology was found to be the FA. Clearly, the most sensitive DTI parameter to the les pathology is λ3, i.e., the minimal diffusivity. Since the QSI and DTI data were obtained from the same acquisition, despite the somewhat higher SNR of the QSI data compared to the DTI data, it seems that the higher diagnostic capacity of the QSI data in this experimental model of dysmyelination, originates mainly from the higher diffusing weighting of the QSI data., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nitrogen (N) enrichment of tropical reefs can result in the dominance of invasive algae. The invasive alga Acanthophora spicifera and the native alga Laurencia nidifica are part of a diverse reef assemblage in 'Ewa Beach, O'ahu. Their N contents and δ(15)N values were investigated to determine if N was enriched and to evaluate potential nitrogenous sources near and removed from storm-drain outlets. δ(15)N values of algae (3.8-17.7‰) were within and above the range for algae around the island (1.9-11.9‰). Elevated algae N isotope values (δ(15)N>+7‰, [N]>1.6%) and seawater nitrate+nitrite levels (0.59-7.93 μM) indicated a mixed, high nutrient environment. The overlap in δ(15)N values with multiple nitrogenous sources precluded identification. However, spatial and temporal patterns did not support stormwater as the dominant, nitrogenous source. Patterns were congruent with algal incorporation of terrestrial derived N, subjected to a high degree of biogeochemical cycling., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In terrestrial ecosystems, plant growth, plant community structure, and ultimately the ecosystem services provided by plants are dependent on the presence and composition of below ground arbuscular mycorrhizal (AM) fungal communities. AM fungi form obligate symbioses with plants providing nutrients to their host plants in exchange for photosynthates. While AM have been found in most wetland ecosystems, the effects of urban contaminants on AM associations are largely unknown. Triclosan (5-chloro-2-[2,4-dichlorophenoxy]phenol; TCS) is a widespread contaminant found in surface waters throughout North America and in addition to antimicrobial properties is purported to have antifungal properties. To determine the effects of TCS on arbuscular mycorrhizal associations, we exposed AM inoculated wetland plant species (Eclipta prostrata, Hibiscus laevis, and Sesbania herbacea) to TCS at concentrations of 0.0, 0.4 and 4.0 μg/L in a continuous flow-through exposure system. TCS exposure caused significant reductions in hyphal and arbuscular colonization while no significant effect was detected for vesicular colonization. Across all species, hyphal colonization was significantly higher in controls (18.58 ± 1.84%) compared to 0.4 and 4.0 μg/L (10.20 ± 1.34% and 9.86 ± 1.32% respectively) TCS treatments. Similarly, arbuscular colonization was significantly higher in the controls (4.58 ± 0.75%) compared to 0.4 μg/L (2.20 ± 0.38%) and 4.0 μg/L (1.22 ± 0.24%) TCS exposures. Since our lowest effect concentration, 0.4 μg/L, lies within the range of concentrations found in North American streams it is plausible that AM colonization has been impacted in streams receiving WWTP effluent. Further studies are required to understand the mechanism of TCS inhibition of mycorrhizal colonization in wetland plant species as well as the potential ecological consequences that a decline in the AM colonization levels may represent., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Primary human hepatocytes are widely used for metabolic stability evaluations. However, there are limited data directly comparing phase I and phase II drug-metabolizing enzymes in fresh and cryopreserved hepatocytes prepared from the same human donor liver. We evaluated the metabolic competency of human hepatocytes prepared from seven donor tissues before and after cryopreservation. Temporal-dependent enzyme activity in suspension and matched adherent cultures of primary human hepatocytes was also assessed. Cryopreservation of hepatocytes resulted in statistically significant increases in activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A but not CYP2C8, CYP2C19, FMO, UGT, and SULT, relative to fresh hepatocytes. In suspension cultures of hepatocytes, enzyme stabilities were as follows: UGT

Patients who present with significant paravalvular regurgitation after mitral valve replacement remain a difficult patient population and high-risk surgical candidates. We present 3 cases of transapical closure of mitral valve paravalvular leak (PVL) after mitral valve replacement using Amplatzer closure devices (AGA Medical Corp, Plymouth, MN). All 3 patients experienced decreased regurgitation at the site of the closure as well as symptomatic improvement in their heart failure., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The copepod, Calanus finmarchicus is a keystone species for the North Atlantic. Because of recent changes in the geographic distribution of this species, there are questions as to how this organism responds physiologically to environmental cues. Molecular techniques allow for examination and new understanding of these physiological changes. Here, we describe the development of a microarray for high-throughput studies of the physiological ecology of C. finmarchicus. An EST database was generated for this species using a normalized cDNA library derived from adult and sub-adult individuals. Sequence data were clustered into contigs and annotated using Blastx. Target transcripts were selected, and unique, 50 base-pair, oligomer probes were generated for 995 genes. Blast2GO processing provided detailed information on gene function. The selected targets included broad representation of biological processes, cellular components, and molecular functions. The microarray was tested in two sets of comparisons: adult females maintained at different food concentrations and field-caught sub-adults showing differences in lipid storage. Up-regulated and down-regulated transcripts were identified for both comparisons. Only a small subset of the genes up-regulated in low food individuals were also up-regulated in lipid-poor animals; no overlap was seen between the genes down-regulated in the two comparisons., (Published by Elsevier Inc.)

The coral reef at Kahekili, Maui is located ~300 m south of the Lahaina Wastewater Reclamation Facility which uses four Class V injection wells to dispose of 3-5 million gallons of wastewater effluent daily. Prior research documented that the wastewater effluent percolates into the nearshore region of Kahekili. To determine if the wastewater effluent was detectable in the surface waters offshore, we used algal bioassays from the nearshore region to 100 m offshore and throughout the water column from the surface to the benthos. These algal bioassays documented that significantly more wastewater effluent was detected in the surface rather than the benthic waters and allowed us to generate a three-dimensional model of the wastewater plume in the Kahekili coastal region. Samples located over freshwater seeps had the highest δ(15)N values (~30-35‰) and the effluent was detected in surface samples 500 m south and 100 m offshore of the freshwater seeps (~8-11‰)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Reports of the effect of low temperatures on ciliary beat frequency (CBF) are conflicting, and the effect on ciliary beat pattern has not been reported. We aimed to clarify this association and determine whether cooling of cilia may allow ciliary function to be assessed without the need of expensive high-speed video microscopy., Methods: Fourteen nasal brush biopsy samples were collected, and the CBF and beat pattern of undisrupted ciliated edges were evaluated. Two methods were used to strictly control changes in temperature: One enabled rapid transitory measurements during cooling and warming, and the other was used to maintain accurate low temperatures over longer periods of time., Results: A sigmoid relationship between CBF and temperature was observed. CBF decreased with cooling and increased with warming. Ciliary function was unaffected by the direction of temperature change and was maintained down to 2°C. The percentage of dyskinetic cilia observed at 2°C or 4°C was unchanged from that at 37°C., Conclusions: Contrary to previous research, our data show that cilia continue to beat with a normal pattern at temperatures as low as 2°C. Slowing of cilia by cooling may allow detailed analysis of ciliary beat pattern without the need of expensive high-speed video microscopy.

A 44-year-old woman presented to our Emergency Department with a 4-day history of severe, sharp left upper quadrant abdominal pain associated with nausea and vomiting. She had been seen 3 days prior at another Emergency Department, and had a negative work-up including a normal non-contrast computed tomography (CT) scan of the abdomen/pelvis for possible kidney stone. Vital signs were: temperature 36.3°C (97.3°F), pulse 100 beats/min, respiratory rate 18 breaths/min, and blood pressure 141/80 mm Hg. Physical examination was remarkable for marked tenderness in the left upper and middle quadrants and voluntary guarding. Bowel sounds were normal. Although laboratory studies were normal, a CT scan of the abdomen/pelvis with intravenous contrast suggested a superior mesenteric artery dissection. This was confirmed with arteriography. The clinical presentation, diagnostic evaluation, and management of superior mesenteric artery dissection are reviewed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Macroalgal blooms of Hypnea musciformis and Ulvafasciata in coastal waters of Maui only occur in areas of substantial anthropogenic nutrient input, sources of which include wastewater effluent via injection wells, leaking cesspools and agricultural fertilizers. Algal delta(15)N signatures were used to map anthropogenic nitrogen through coastal surveys (island-wide and fine-scale) and algal deployments along nearshore and offshore gradients. Algal delta(15)N values of 9.8 per thousand and 2.0-3.5 per thousand in Waiehu and across the north-central coast, respectively, suggest that cesspool and agricultural nitrogen reached the respective adjacent coastlines. Effluent was detected in areas proximal to the Wastewater Reclamation Facilities (WWRF) operating Class V injection wells in Lahaina, Kihei and Kahului through elevated algal delta(15)N values (17.8-50.1 per thousand). From 1997 to 2008, the three WWRFs injected an estimated total volume of 193 million cubic meters (51 billion gallons) of effluent with a nitrogen mass of 1.74 million kilograms (3.84 million pounds)., ((c) 2009 Elsevier Ltd. All rights reserved.)

Background: Current implantable left ventricular assist devices (LVAD) improve survival and function for patients with very late stage heart failure (HF) but may also offer benefit before inotrope dependence. Debate continues about selection of HF patients for LVAD therapy. We sought to determine what level of personal risk and disability HF patients thought would warrant LVAD therapy., Methods: The study included 105 patients with symptomatic HF and an LV ejection fraction (EF) < 35% who were given a written paragraph about LVADs and asked about circumstances under which they would consider such a device. New York Heart Association (NYHA) functional class, time trade-off utility, and patient-assessed functional score were determined., Results: Participants (mean age, 58 years) had an LVEF of 21%. The median duration of HF was 5 years, and 65% had a primary prevention implantable cardioverter defibrillator. Presented with a scenario of bed-ridden HF, 81% stated they would definitely or probably want an LVAD; 50% would consider LVAD to prolong survival if HF survival were predicted to be < 1 year and 75% if < 6 months. Meanwhile, 44% would consider LVAD if they could only walk < 1 block and 64% if they could not dress without stopping. Anticipated thresholds did not differ by NYHA class, time trade-off, or functional score., Conclusions: Patient thresholds for LVAD insertion parallel objective survival and functional data. HF patients would be receptive to referral for discussion of LVAD by the time expected mortality is within 6 to 12 months and activity remains limited to less than 1 block.

Purpose: This focus group study describes motivators and barriers to participation in the Mayo Mammography Health Study (MMHS), a large-scale longitudinal study examining the causal association of breast density with breast cancer, involving completion of a survey, providing access to a residual blood sample for genetic analyses, and sharing their results from a screening mammogram. These women would then be followed up long term for breast cancer incidence and mortality., Methods: Forty-eight women participated in six focus groups, four with MMHS non-respondents (n = 27), and two with MMHS respondents (n = 21). Major themes were summarized using content analysis. Social cognitive theory (SCT) was used as a framework for interpretation of the findings., Results: Barriers to participation among MMHS non-respondents were 1) lack of confidence in their ability to fill out the survey accurately (self-efficacy); 2) lack of perceived personal connection to the study or value of participation (expectancies); and 3) fear related to some questions about perceived cancer risk and worry/concern (emotional coping responses). Among MMHS respondents, personal experience with cancer was reported as a primary motivator for participation (expectancies)., Conclusions: Application of a theoretical model such as social cognitive therapy to the development of a study recruitment plan could be used to improve rates of study participation and provide a reproducible and evaluable strategy.

Platelet-rich plasma has been shown in several in vitro and animal studies to play a role in promoting new bone formation. A systematic literature review was conducted to identify the current relevant evidence base, searching across multiple sources including Medline, Embase and the Cochrane Library, and finding five clinically relevant articles. Only one was a randomised controlled trial, but this was underpowered for the outcome measure defined. Three studies exclusively concerned children, and included those with congenital limb deformities. Two other reports were case series. Early clinical results suggest that the use of platelet-rich plasma is safe and feasible, but that at present there is no clinical evidence of benefit in either acute or delayed fracture healing.

Two partial mRNA sequences predicted to encode anti-lipopolysaccharide factors (ALFs) were identified among expressed sequence tags generated from the American lobster Homarus americanus and complete cDNA sequences were obtained from library clones. Comparison of the translated amino acid sequences to those publicly available confirmed similarity to arthropod anti-lipopolysaccharide factors. Both protein sequences, designated ALFHa-1 and ALFHa-2, contained an N-terminal signal peptide and two half-cysteines participating in a disulfide bridge, features conserved in other ALFs. Predicted secondary structures were similar to that described for the ALF from the horseshoe crab Limulus polyphemus. As part of an exploratory study of immunity in H. americanus, lobsters were injected with the bacterium Vibrio fluvialis and gill, hematopoietic, and hepatopancreas tissues were sampled for analysis of gene expression of ALFHa-1 and ALFHa-2 by quantitative PCR. The relative abundance of ALFHa-2 mRNA was not significantly affected by Vibrio injection in any of the three tissues tested. In contrast, ALFHa-1 mRNA levels in gills were increased by the treatment some 17-fold. Our results support a molecularly specific regulation of antimicrobial proteins in response to bacterial infection in H. americanus., (2008 Elsevier Inc. All rights reserved.)

The zebrafish enteric nervous system (ENS), like those of all other vertebrate species, is principally derived from the vagal neural crest cells (NCC). The developmental controls that govern the migration, proliferation and patterning of the ENS precursors are not well understood. We have investigated the roles of endoderm and Sonic hedgehog (SHH) in the development of the ENS. We show that endoderm is required for the migration of ENS NCC from the vagal region to the anterior end of the intestine. We show that the expression of shh and its receptor ptc-1 correlate with the development of the ENS and demonstrate that hedgehog (HH) signaling is required in two phases, a pre-enteric and an enteric phase, for normal ENS development. We show that HH signaling regulates the proliferation of vagal NCC and ENS precursors in vivo. We also show the zebrafish hand2 is required for the normal development of the intestinal smooth muscle and the ENS. Furthermore we show that endoderm and HH signaling, but not hand2, regulate gdnf expression in the intestine, highlighting a central role of endoderm and SHH in patterning the intestine and the ENS.